No Identical “Mesenchymal Stem Cells” at Different Times and Sites: Human Committed Progenitors of Distinct Origin and Differentiation Potential Are Incorporated as Adventitial Cells in Microvessels
Open accessAbstract
A widely shared view reads that mesenchymal stem/stromal cells ("MSCs") are ubiquitous in human connective tissues, can be defined by a common in vitro phenotype, share a skeletogenic potential as assessed by in vitro differentiation assays, and coincide with ubiquitous pericytes. Using stringent in vivo differentiation assays and transcriptome analysis, we show that human cell populations from different anatomical sources, regarded as "MSCs" based on these criteria and assumptions, actually differ widely in their transcriptomic signature and in vivo differentiation potential. In contrast, they share the capacity to guide the assembly of functional microvessels in vivo, regardless of their anatomical source, or in situ identity as perivascular or circulating cells. This analysis reveals that muscle pericytes, which are not spontaneously osteochondrogenic as previously claimed, may indeed coincide with an ectopic perivascular subset of committed myogenic cells similar to satellite cells. Cord blood-derived stromal cells, on the other hand, display the unique capacity to form cartilage in vivo spontaneously, in addition to an assayable osteogenic capacity. These data suggest the need to revise current misconceptions on the origin and function of so-called "MSCs," with important applicative implications. The data also support the view that rather than a uniform class of "MSCs," different mesoderm derivatives include distinct classes of tissue-specific committed progenitors, possibly of different developmental origin.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Only BM vessel-residing cells defined as pericytes have the ability to differentiate into osteoblasts during physiological bone remodeling.
“Nevertheless, Sacchetti et al.276 pointed out that only BM vessel-residing cells defined as pericytes have the ability to differentiate into osteoblasts during physiological bone remodeling.”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [276]
Mesenchyme-derived precursors can give rise to any mesenchyme-derived tissue type including bone, cartilage, muscle, tendon, ligament, and fat tissue.
“there is high plausibility that these precursors can give rise to any mesenchyme-derived tissue type including e.g., bone, cartilage, muscle, tendon, ligament, and fat tissue [98,99,100].”
From Interactions between Muscle and Bone—Where Physics Meets Biology (2020) · cites this paper as [100]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
Multilineage potential of adult human mesenchymal stem cells
Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., & Marshak, D. R. (1999) · Science · doi:10.1126/science.284.5411.143 · Cited by 21,052 · see citing works
Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F. C., Krause, D. S., Deans, R. J., Keating, A., Prockop, D. J., & Horwitz, E. M. (2006) · Cytotherapy · doi:10.1080/14653240600855905 · Cited by 17,766 · see citing works
Caplan, A. I. (1991) · Journal of Orthopaedic Research® · doi:10.1002/jor.1100090504 · Cited by 6,563 · see citing works
Stöckl, S., Göttl, C., Grifka, J. K., & Grässel, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350089 · Cited by 4,670 · see citing works
A perivascular origin for mesenchymal stem cells in multiple human organs
Crisan, M., Yap, S., Casteilla, L., Chen, C.-W., Corselli, M., Park, T. S., Andriolo, G., Sun, B., Zheng, B., Zhang, L., et al. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.07.003 · Cited by 3,991 · see citing works
Pericytes: Developmental, Physiological, and Pathological Perspectives, Problems, and Promises
Armulik, A., Genové, G., & Betsholtz, C. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.07.001 · Cited by 2,653 · see citing works
Molecular regulation of vessel maturation
Jain, R. K. (2003) · Nature Medicine · doi:10.1038/nm0603-685 · Cited by 2,515 · see citing works
Mesenchymal stem cells reside in virtually all post-natal organs and tissues
Meirelles, L. D. S., Chagastelles, P. C., & Nardi, N. B. (2006) · Journal of Cell Science · doi:10.1242/jcs.02932 · Cited by 2,488 · see citing works
Pericyte Loss and Microaneurysm Formation in PDGF-B-Deficient Mice
Lindahl, P., Johansson, B. R., Levéen, P., & Betsholtz, C. (1997) · Science · doi:10.1126/science.277.5323.242 · Cited by 2,226 · see citing works
Sacchetti, B., Funari, A., Michienzi, S., Di Cesare, S., Piersanti, S., Saggio, I., Tagliafico, E., Ferrari, S., Robey, P. G., Riminucci, M., et al. (2007) · Cell · doi:10.1016/j.cell.2007.08.025 · Cited by 2,226 · see citing works
Self-citationHellström, M., Kalén, M., Lindahl, P., Abramsson, A., & Betsholtz, C. (1999) · Development · doi:10.1242/dev.126.14.3047 · Cited by 1,702 · see citing works
Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis
Joe, A. W. B., Yi, L., Natarajan, A., Le Grand, F., So, L., Wang, J., Rudnicki, M. A., & Rossi, F. M. V. (2010) · Nature Cell Biology · doi:10.1038/ncb2015 · Cited by 1,690 · see citing works
Caplan, A. I., & Correa, D. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2011.06.008 · Cited by 1,682 · see citing works
Mesenchymal Stem Cells: Revisiting History, Concepts, and Assays
Bianco, P., Robey, P. G., & Simmons, P. J. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.03.002 · Cited by 1,625 · see citing works
Self-citationBianco, P., Cao, X., Frenette, P. S., Mao, J. J., Robey, P. G., Simmons, P. J., & Wang, C.-Y. (2013) · Nature Medicine · doi:10.1038/nm.3028 · Cited by 1,199 · see citing works
Self-citationDirect Isolation of Satellite Cells for Skeletal Muscle Regeneration
Montarras, D., Morgan, J., Collins, C., Relaix, F., Zaffran, S., Cumano, A., Partridge, T., & Buckingham, M. (2005) · Science · doi:10.1126/science.1114758 · Cited by 1,100 · see citing works
Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5‐azacytidine
Wakitani, S., Saito, T., & Caplan, A. I. (1995) · Muscle & Nerve · doi:10.1002/mus.880181212 · Cited by 1,081 · see citing works
Kögler, G., Sensken, S., Airey, J. A., Trapp, T., Müschen, M., Feldhahn, N., Liedtke, S., Sorg, R. V., Fischer, J., Rosenbaum, C., et al. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040440 · Cited by 1,029 · see citing works
Self-citationPericytes of human skeletal muscle are myogenic precursors distinct from satellite cells
Dellavalle, A., Sampaolesi, M., Tonlorenzi, R., Tagliafico, E., Sacchetti, B., Perani, L., Innocenzi, A., Gálvez, B. G., Messina, G., Roberta Morosetti, A., et al. (2007) · Nature Cell Biology · doi:10.1038/ncb1542 · Cited by 1,001 · see citing works
Self-citationPericytes in the microvasculature
Hirschi, K. K., & D'Amore, P. A. (1996) · Cardiovascular Research · doi:10.1016/s0008-6363(96)00063-6 · Cited by 763 · see citing works
Caplan, A. I. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.08.008 · Cited by 695 · see citing works
Díaz‐Flores, L., Gutiérrez, R., Madrid, J. F., Varela, H., Valladares, F., Acosta, E., Martı́n-Vasallo, P., & Díaz-Flores, L. (2009) · PubMed · doi:10.14670/hh-24.909 · Cited by 547 · see citing works
Minasi, M. G., Riminucci, M., De Angelis, L., Borello, U., Berarducci, B., Innocenzi, A., Caprioli, A., Sirabella, D., Baiocchi, M., De Maria, R., et al. (2002) · Development · doi:10.1242/dev.129.11.2773 · Cited by 514 · see citing works
Self-citationIsolation of Adult Mouse Myogenic Progenitors
Sherwood, R. I., Christensen, J. L., Conboy, I. M., Conboy, M. J., Rando, T. A., Weissman, I. L., & Wagers, A. J. (2004) · Cell · doi:10.1016/j.cell.2004.10.021 · Cited by 491 · see citing works
Krebsbach, P. H., Kuznetsov, S. A., Satomura, K., Emmons, R. V. B., Rowe, D. W., & Robey, P. G. (1997) · Transplantation · doi:10.1097/00007890-199704270-00003 · Cited by 480 · see citing works
Self-citationMitchell, K. J., Pannérec, A., Cadot, B., Parlakian, A., Besson, V., Gomes, E. R., Marazzi, G., & Sassoon, D. A. (2010) · Nature Cell Biology · doi:10.1038/ncb2025 · Cited by 442 · see citing works
Bianco, P., & Robey, P. G. (2015) · Development · doi:10.1242/dev.102210 · Cited by 402 · see citing works
Self-citationBianco, P. (2014) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100913-013132 · Cited by 400 · see citing works
Self-citationReinisch, A., Etchart, N., Thomas, D., Hofmann, N., Frühwirth, M., Sinha, S., Chan, C. K. F., Senarath-Yapa, K., Seo, E. Y., Wearda, T. L., et al. (2014) · Blood · doi:10.1182/blood-2014-04-572255 · Cited by 270 · see citing works
Bone and the hematopoietic niche: a tale of two stem cells
Bianco, P. (2011) · Blood · doi:10.1182/blood-2011-01-315069 · Cited by 253 · see citing works
Self-citationFriedenstein, A. J., Latzinik, N. V., Grosheva, A. G., & Gorskaya, U. F. (1982) · PubMed · Cited by 234 · see citing works
Oxygen Tension Regulates Chondrocyte Differentiation and Function during Endochondral Ossification
Hirao, M., Tamai, N., Tsumaki, N., Yoshikawa, H., & Myoui, A. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602296200 · Cited by 192 · see citing works
Smooth muscle of the dorsal aorta shares a common clonal origin with skeletal muscle of the myotome
Ešner, M., Meilhac, S. M., Relaix, F., Nicolas, J.-F., Cossu, G., & BUCKINGHAM, M. E. (2006) · Development · doi:10.1242/dev.02226 · Cited by 158 · see citing works
Self-citationHuman papillomavirus in a necessary cause of invasive cervical cancer worldwide
(1999) · Pure Amsterdam UMC · doi:10.1002/(sici)1096-9896(199909)189:1 · Cited by 140 · see citing works
Piersanti, S., Remoli, C., Saggio, I., et al. (2009) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.091036 · Cited by 98 · see citing works
Self-citationBosch, J., Houben, A. P., Radke, T. F., Stapelkamp, D., Bünemann, E., Balan, P., Buchheiser, A., Liedtke, S., & Kögler, G. (2011) · Stem Cells and Development · doi:10.1089/scd.2011.0414 · Cited by 97 · see citing works
Self-citationPhillips, M., Kuznetsov, S. A., Cherman, N., Park, K., Chen, K. G., McClendon, B. N., Hamilton, R. S., McKay, R. D. G., Chenoweth, J. G., Mallon, B. S., et al. (2014) · Stem Cells Translational Medicine · doi:10.5966/sctm.2013-0154 · Cited by 92 · see citing works
Self-citationLiedtke, S., Buchheiser, A., Bosch, J., et al. (2010) · Stem Cell Research · doi:10.1016/j.scr.2010.03.004 · Cited by 76 · see citing works
Self-citationKluth, S. M., Buchheiser, A., Houben, A. P., Geyh, S., Krenz, T., Radke, T. F., Wiek, C., Hanenberg, H., Reinecke, P., Wernet, P., et al. (2010) · Stem Cells and Development · doi:10.1089/scd.2010.0070 · Cited by 70 · see citing works
Ragni, E., Montemurro, T., Montelatici, E., Lavazza, C., Viganò, M., Rebulla, P., Giordano, R., & Lazzari, L. (2013) · Experimental Cell Research · doi:10.1016/j.yexcr.2013.04.002 · Cited by 48 · see citing works
Kaltz, N., Funari, A., Hippauf, S., et al. (2008) · Stem Cells · doi:10.1634/stemcells.2008-0304 · Cited by 45 · see citing works
Self-citationLiedtke, S., Sacchetti, B., Laitinen, A., et al. (2016) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2167 · Cited by 9 · see citing works
Self-citationMechanisms of Myogenic Specification and Patterning
Applebaum, M., & Kalcheim, C. (2014) · Results and problems in cell differentiation · doi:10.1007/978-3-662-44608-9_4 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Viswanathan, S., Shi, Y., Galipeau, J., Krampera, M., Leblanc, K., Martin, I., Nolta, J., Phinney, D. G., & Sensebe, L. (2019) · Cytotherapy · doi:10.1016/j.jcyt.2019.08.002 · Cited by 839 · see citing works
Bone remodeling: an operational process ensuring survival and bone mechanical competence
Bolamperti, S., Villa, I., & Rubinacci, A. (2022) · Bone Research · doi:10.1038/s41413-022-00219-8 · Cited by 482 · see citing works
Interactions between Muscle and Bone—Where Physics Meets Biology
Herrmann, M., Engelke, K., Ebert, R., Müller-Deubert, S., Rudert, M., Ziouti, F., Jundt, F., Felsenberg, D., & Jakob, F. (2020) · Biomolecules · doi:10.3390/biom10030432 · Cited by 197 · see citing works
Role of MSC in the Tumor Microenvironment
Hass, R. (2020) · Cancers · doi:10.3390/cancers12082107 · Cited by 116 · see citing works
Lei, L., Bruneau, A., El Mourabit, H., Guégan, J., Folseraas, T., Lemoinne, S., Karlsen, T. H., Hoareau, B., Morichon, R., Gonzalez‐Sanchez, E., et al. (2022) · Hepatology · doi:10.1002/hep.32456 · Cited by 94 · see citing works
Qadan, M. A., Piuzzi, N. S., Boehm, C., Bova, W., Moos, M., Midura, R. J., Hascall, V. C., Malcuit, C., & Muschler, G. F. (2018) · Cytotherapy · doi:10.1016/j.jcyt.2017.11.013 · Cited by 32 · see citing works
- Authors
- Sacchetti, B., Funari, A., Remoli, C., Giannicola, G., Kogler, G., Liedtke, S., Cossu, G., Serafini, M., Sampaolesi, M., Tagliafico, E., Tenedini, E., Saggio, I., Robey, P. G., Riminucci, M., & Bianco, P.
- Affiliations
- Sapienza University of Rome (IT)
- Heinrich Heine University Düsseldorf (DE)
- University of Manchester (GB)
- Dulbecco Telethon Institute (IT)
- KU Leuven (BE)
- University of Modena and Reggio Emilia (IT)
- National Institutes of Health (US)
- Corresponding author
- Robey, Pamela G.
- Riminucci, Mara
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 6
- Issue
- 6
- Pages
- 897-913
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC4912436
- OpenAlex
- W2427154682
- Cited by
- 428
- References
- 44
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 27 · 2023: 41 · 2022: 50 · 2021: 44 · 2020: 68 · 2019: 58 · 2018: 51 · 2017: 55 · 2016: 8
- FWCI
- 41.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Lirias (submittedVersion, cc-by-nc-nd)
- BOA (University of Milano-Bicocca) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
- Research Explorer (The University of Manchester) (submittedVersion, cc-by)
- Funders
- Fondazione Telethon (GGP09227)
- National Institutes of Health
- Ministero della Salute
- U.S. Department of Health and Human Services
- Ministero dell’Istruzione, dell’Università e della Ricerca
- National Institute of Dental and Craniofacial Research
- Sapienza Università di Roma (DFG - KO2119/8-1, TCP07004)
- Istituto Pasteur-Fondazione Cenci Bolognetti
- International Foundation for Research in Paraplegia
- European Commission
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- mesenchymal stem cells, stromal cells, pericytes, adventitial cells, perivascular cells, satellite cells, myogenic progenitor cells, chondrogenesis, osteogenic differentiation, osteochondrogenic differentiation, gene expression signatures, cell of origin
- MeSH terms
- Animals, Bone Marrow Cells, Cell Differentiation, Fetal Blood, Humans, Osteogenesis, Phenotype, Transplantation, Heterologous, Biomarkers, Gene Expression, Cell Lineage, Chondrogenesis, Pericytes, Gene Expression Profiling, Satellite Cells, Skeletal Muscle, Mesenchymal Stem Cell Transplantation, Mice, Microvessels, Transcriptome, Mesenchymal Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
